Vesicle trafficking is defined as the vesicular transport of materials between different subcellular compartments of eukaryotic cells. Vesicles bud from a donor membrane and fuse with a recipient one carrying internalized materials from one site to another. Several protein complexes involving integral proteins of the vesicle and target membranes, such as Sec proteins and Rab proteins, help regulate vesicular transport by directing the vesicles to and from the correct membrane surface.
Sec1 is a member of a family of proteins which mediate vesicle trafficking. The Sec1 family consists of four members, Sec1, Vps33, Vps45, and Sly1. Specifically, Sec1 regulates transport from the endoplasmic reticulum (ER) to the Golgi complex; Vps33 participates in transport from a prevacuolar compartment to the vacuole; Vps45 is essential for transport from the Golgi to a prevacuolar compartment; and Sly1 is involved in transport from the ER to the Golgi. The yeast Sec1 proteins are hydrophilic, 80 kDa in size, and have about 20-24% sequence identity (Aalto, M. et al. (1992) Cell 68: 181-182). Rat Sec1, a mammalian homolog of the yeast Sec1, binds syntaxin, a plasma membrane protein localized in the active zone of axon terminals and essential for synapsis. Rat Vps33a and Vps33b and human Vps45, however, do not bind any of the known syntaxins. Northern analysis shows that rat Vps33, rat Vps45 and human Vps45 are expressed in brain, spleen, lung, liver, skeletal muscle, kidney, and testis. These results suggest that the mammalian proteins are essential in mediating transport among the Golgi complex, synaptic vesicles, prelysosomal compartments, and the lysosome (El-Husseini, A. E.-D. et al. (1997) Biochim. Biophys. Acta 1325: 8-12; and Pevsner, J. et al. (1996) Gene 183: 7-14).
Assembly protein complexes (APs) are essential for the assembly of clathrin-coated vesicles which participate in intracellular vesicle transport and receptor-mediated endocytosis. APs consist of two classes of homologous heterotetrameric complexes, AP-1 and AP-2, each of which is composed of two large chains, a medium chain, and a small chain. AP-1 functions in the Golgi complex, and AP-2 is localized in the plasma membrane and on the surface of endosomes. Avian px19 is an AP-small-chain homolog and possesses the LEA (late embryogenesis abundant) motif found in plant seed proteins. Developmental data suggest that px19 may be involved in hematopoiesis during avian development (Niu, S. et al. (1996) Gene 175: 187-191).
Non-clathrin-coated vesicles function in transporting proteins from the ER to the Golgi. These vesicles are coated with a family of AP-homologous proteins, the COP-proteins, which exist in the cytosol of eukaryotic cells as a complex, named coatomer. The ζ subunit of the COP coatomer is 20 kDa and has sequence similarity to the small chains of the AP complexes. Unlike other coatomer subunits, ζCOP is found in both coatomer-bound and coatomer-free cell extract fractions. Polyclonal antibody specific for ζCOP blocks the binding of the coatomer to the Golgi membrane, and thereby prevents the assembly of COP-coated vesicles on the Golgi cisternae (Kuge, O. et al. (1993) J. Cell Biol. 123: 1727-1734).
The discovery of three new human vesicle trafficking proteins and the polynucleotides encoding them satisfies a need in the art by providing new compositions which are useful in the diagnosis, prevention, and treatment of inflammation and disorders associated with cell proliferation and apoptosis.